Fighting the superbugs turning the tide of antimicrobial resistance

Transcription

1 Fighting the superbugs turning the tide of antimicrobial resistance

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3 Human mortality burden AVIAN FLU H5N1 449 ANTIBIOTIC RESISTANCE > EBOLA 11,298 SWINE FLU H1N

4 AMR is a costly and ticking time bomb

5 The microbiome - our best friend

6 Antibiotic consumption EU tons Human use 52% Animal use 48% 80 % out-patients 20 % hospital Björn Wullt, DGU 2015

7 Selective pressure Antimicrobial resistance is the sum of all antimicrobial use The only weapon we have to not lose the control is to take the control Diaz Högberg, REACT

8 Sharing is everything..

9 Horizontal gene transfer à sharing of DNA à Antibiotic resistance Transformation DNA Pili Bacterium

10 Horizontal gene transfer à sharing of DNA à Antibiotic resistance DNA hitch-hikes on retracting pili At 10x speed At 5x speed Mediating bacterial sex Skerker & Berg,

11 Transduction Transfer of bacterial DNA via viruses: bacteriophages inject DNA

12 Conjugation Transfer of bacterial DNA by contact between bacteria: sex pili, cell-to-cell contact

13 Can AMR arise without transfer of DNA? DNA damage events and defects in DNA repair allow chromosomal mutations to arise

14 How did we get here? Selective pressure: Antibiotics

15 Ex 1: What happened with gonorrhoea?

16 Gonorrhoea superbug story Clin Microbiol Rev 27(3): , 2014

17 Gonorrhoea superbug story Transformation AND conjugation Selective pressure: resistance against both narrow- and broadspecter drugs AMR required change of clinical guidelines multiple time in the last 2 years We re nearly out of juice

18 Example 2: Tuberculosis Mycobacterium tuberculosis colonizes 1/3 of the world s population 9 million new cases yearly 1.5 mill deaths yearly MDR à XDR Already in 2012: >10% of Mtb strains in Europe were XDR (WHO, 2015)

19 How do MDR/XDR Mtb cells arise? DNA damage events and defects in DNA repair contribute to mutations arising under selective pressure à resistance: MDR à XDR, no treatment Selective pressure, poor hygiene, poor compliance, migration, travel, alarming reduction in development of novel drug candidates filling up biosafety facilities

20 How do we solve the AMR problem? Turning the tide of AMR =TTA

21 From the patient to global health

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23 Structure-function analysis: Construction and in vivo expression of complex-components/mutants Large-scale complex purification 3D cryoem and single particle averaging

24 Big data generated in the omics era Genomics: The origin! Transcriptomics: What s happening? Proteomics: What happened! PTMs: How are proteins decorated?

25 New einfrastructure for cloud computing Big data à require large internal memory and vast storage capacity einfrastructure for handling large data sets: All scientists involved can share and analyse large data-sets at the same time

26 Novel diagnostics Diagnostics and surveillance of AMR: New and improved diagnostics of AMR and antibiotics on a chip

27 New drugs for super-bugs Therapeutics: Novel antibiotics / new principles for treatment

28 Novel prevention and intervention New vaccines Block transmission and DNA transfer pathways Surveillance is intervention Impact of the microbiomes and probiotics/fecal transplantation

29 - turn your tide!